甘草查尔酮A在比格犬体内的药代动力学研究

Pharmacokinetics of licochalcone A in Beagle dogs

目的建立测定比格犬血浆中甘草查尔酮A含量的UPLC-MS/MS分析方法,并研究甘草查尔酮A单剂量静脉注射和灌胃给药后在比格犬体内药代动力学模式。方法比格犬以3 mg·kg^(-1)的剂量分别进行静脉注射和灌胃给药甘草查尔酮A,采集不同时间点的血浆样品,采用UPLC-MS/MS方法测定血浆中甘草查尔酮A的浓度,采用DAS 2.1.1版软件对血药浓度-时间曲线进行统计矩拟合,计算甘草查尔酮A的药代动力学参数。结果血浆中甘草查尔酮A的线性回归方程为:Y=0.039X+0.1959,R^(2)=0.9997,线性范围为2~2000μg·L^(-1)。静脉注射甘草查尔酮A在血浆中的半衰期t_(1/2)为6.57 h,药时曲线下面积(AUC0~t)为1665 h·mg·L^(-1),平均驻留时间(MRT0~t)为5.68 h,清除率(CL)为2106 L·h^(-1)·kg^(-1)。灌胃给药甘草查尔酮A在血浆中的t_(1/2)为8.23 h,AUC0~t为397 h·mg·L^(-1),MRT0~t为9.35 h,口服生物利用度为23.8%。结论甘草查尔酮A在血浆的UPLC-MS/MS方法具有良好的专属性与灵敏度。灌胃给药甘草查尔酮A具有良好的血浆暴露量及口服生物利用度。

Objective To develop an UPLC-MS/MS to determine the concentration of licochalcone A in the plasma of Beagle dogs and the pharmacokinetics after a single dose intravenous and oral administration of licochalcone A,respectively.Methods Beagle dogs were intravenously and orally administered licochalcone A(3 mg·kg^(-1)).The plasma samples were collected at different time spots.UPLC-MS/MS was used to determine the concentration of licochalcone A in the plasma.The plasma concentration-time curves were fit by DAS 2.1.1 software to determine the pharmacokinetic parameters of licochalcone A.Results The linear regression of licochalcone A in the plasma was:Y=0.039X+0.1959,R^(2)=0.9997,and the linear range was 2~2000μg·L^(-1).In the intravenous administration model,the half-life(t_(1/2))of licochalcone A in the plasma was 6.57 h,the area under the drug-time curve(AUC0~t)was 1665 h·mg·L^(-1),the mean residence time(MRT0~t)was 5.68 h,and the clearance rate(CL)was 2106 L·h^(-1)·kg^(-1).While in the oral administration model,the t_(1/2)of licochalcone A in the plasma was 8.23 h,AUC0~t was 397 h·mg·L^(-1),the MRT0~t was 9.35 h,and the oral bioavailability was 23.8%.Conclusion The UPLC-MS/MS method is accurate and applicable for the pharmacokinetic study of licochalcone A in the plasma of Beagle dogs.Licochalcone A shows moderate oral bioavailability.